Benoxaprofen is effective in the systemic treatment of psoriasis but is toxic. One of the goals of this application is to modify benoxaprofen for topical administration which should result in high concentrations at the lesion site, lower concentrations systemically, and improved safety. Thirteen compounds have been evaluated in the arachidonic acid mouse ear inflammation assay. Four of our compounds are more active than benoxaprofen in this model. 3890902 was more active (0.2<ED50<2 mumol/ear) than the reference compound, nordihydroguaiaretic acid, which showed a 49% inhibition at 10 mumol/ear. A hypothesis is proposed for drug design that is based on structural similarity between some synthetic lipoxygenase inhibitors and an endogenous immunosuppressive agent. We propose to use computer-aided drug design methodologies to optimize our most active compounds. In Phase II thirty compounds based on 5-lipoxygenase inhibitors and/or derived from benoxaprofen will be synthesized and evaluated in the mouse ear model and the 5-lipoxygenase assay.